Local health systems are increasingly tasked to play a more central role in driving action to reduce social inequalities in health. Past experience, however, has demonstrated the challenge of reorienting health system actions towards prevention and the wider determinants of health. In this review, I use meta-ethnographic methods to synthesise findings from eleven qualitative research studies that have examined how ambitions to tackle social inequalities in health take shape within local health systems. The resulting line-of-argument illustrates how such inequalities continue to be problematised in narrow and reductionist ways to fit both with pre-existing conceptions of health, and the institutional practices which shape thinking and action. Instances of health system actors adopting a more social view of inequalities, and taking a more active role in influencing the social and structural determinants of health, were attributed to the beliefs and values of system leaders, and their ability to push-back against dominant discourses and institutional norms. This synthesised account provides an additional layer of understanding about the specific challenges experienced by health workforces when tasked to address this complex and enduring problem, and provides essential insights for understanding the success and shortcomings of future cross-sectoral efforts to tackle social inequalities in health.Supplementary informationThe online version contains supplementary material available at 10.1057/s41285-022-00176-6.